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Hepatocellular carcinoma (HCC)

Overview

Hepatocellular carcinoma (HCC) is the most common type of liver cancer. It generally occurs as result of abnormal growth of hepatocytes—the liver's main cells—and often develops in the background of chronic liver disease or cirrhosis. The prognosis for HCC (disease outcome, e.g., cure, relapse, etc.) depends on factors such as tumour size, liver function, presence of metastasis, and the underlying liver disease. Early stage HCC has a better prognosis, particularly if treated with surgery (or a liver transplant). Advanced HCC has a poorer prognosis, but new systemic therapies have improved the treatment outcomes in some patients.

Several factors increase the risk of developing HCC; these include:

  • Chronic viral hepatitis: Hepatitis B virus (HBV) and Hepatitis C virus (HCV) infections are the leading causes of HCC worldwide, particularly in regions with high prevalence of these viruses.
  • Cirrhosis: ALD and N/AFLD—both leading to cirrhosis—are significant risk factors.
  • Aflatoxin exposure: Exposure to aflatoxins (produced by certain moulds found in poorly stored grains and nuts) can increase the risk of HCC, especially in regions like sub-Saharan Africa and Southeast Asia.
  • Metabolic disorders: Conditions like hemochromatosis (iron overload), alpha-1 antitrypsin deficiency, and Wilson's disease can increase HCC risk.
  • Obesity and type 2 diabetes: Obesity and diabetes often contribute to the development of N/AFLD, which in turn increases HCC risk.
  • Family history: A family history of liver cancer or inherited liver diseases may increase HCC risk.
  • Age and gender: HCC is more common in older adults and is more frequent in men than in women.
  • Smoking: Smoking can increase the likelihood of developing HCC, particularly in individuals with preexisting liver disease.

In early stages, the symptoms of HCC may be apparent, but as the disease progresses, symptoms can become apparent; these include:

  • Abdominal pain or discomfort (especially in the upper right side of the abdomen).
  • Unexplained weight loss
  • Loss of appetite
  • Jaundice
  • Fatigue
  • Swelling of the abdomen (due to fluid buildup)
  • Nausea and vomiting
  • Fever
  • Easy bruising or bleeding (due to liver dysfunction)

HCC is typically diagnosed through a combination of clinical, imaging, and laboratory tests; these include:

  • Imaging studies:
    • Ultrasound: This is generally the first imaging modality to be used to detect liver masses (tumours).
    • CT or MRI: These provide detailed information about tumour size and location and extent of cancer spread.
    • Contrast-enhanced imaging (CT/MRI): This imaging modality can help differentiate HCC from benign (non-cancerous) lesions.
  • Blood tests:
    • Alpha-fetoprotein (AFP): Elevated levels of AFP can indicate HCC; however, it should be noted that other cancers can also elevate AFP levels.
    • Liver function tests: Individuals with damaged livers (including those with cancer) have elevated levels of ALT, AST, ALP, and bilirubin and low albumin levels.
    • Hepatitis markers: If a patient has a history of hepatitis, testing for HBV and HCV is important.
  • Liver biopsy: A biopsy, though less commonly performed, may be done if imaging findings are inconclusive or if there is uncertainty in diagnosis.
  • Endoscopy: In cases where cirrhosis is present, an endoscopy may be done to check for varices or signs of liver damage.

The treatment of HCC depends on the stage of the cancer, liver function, and the patient’s overall health. Treatment options include:

  • Surgical treatment:
    • Liver resection: Tumour-removal surgery may be an option if the tumour is confined to a particular part of the liver and the liver function is normal.
    • Liver transplantation: For patients with cirrhosis or large tumours, liver transplantation may be considered as severe liver and liver failure are a reality in these patients.
  • Ablation therapy: This is an umbrella term to describe minimally invasive surgical procedures (involving the use of very tiny cuts to perform surgery) that destroy small tumours.
    • Percutaneous ethanol injection (PEI)
    • Radiofrequency ablation (RFA)
  • Transarterial chemoembolization (TACE): TACE is used for patients who are not candidates for surgery. It involves delivering chemotherapy directly to the tumour while blocking the blood supply.
  • Systemic therapies: These therapies generally affect the entire body.
    • Targeted therapy: Drugs like sorafenib or lenvatinib that target cancer cell growth may be used for advanced HCC.
    • Immunotherapy: Drugs such as nivolumab or pembrolizumab (immune checkpoint inhibitors) have shown effectiveness in some patients with advanced or metastatic HCC.
    • Radiation therapy: In some cases, an external beam of radiation may be used to kill cancer cells, particularly when other treatments are not suitable.
    • Chemotherapy: Chemotherapy is generally not effective for HCC, so it is rarely used.
  • Palliative care: For advanced cases of HCC, the treatment focuses on relieving symptoms, improving quality of life, and managing complications like ascites or bleeding.

Strategies to prevent HCC occurrence include:

  • Vaccination against Hepatitis B virus.
  • Screening for liver disease in at-risk populations (e.g., patients with hepatitis B, hepatitis C, or cirrhosis).
  • Managing chronic liver disease (avoiding alcohol, controlling obesity, and treating hepatitis).
  • Healthy lifestyle choices (maintaining a healthy weight, avoiding tobacco, and managing diabetes).
  • Regular screening (e.g., ultrasound and AFP levels) for individuals at high risk of HCC.
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